Parkin-Dependent Mitophagy is Required for the Inhibition of ATF4 on NLRP3 Inflammasome Activation in Cerebral Ischemia-Reperfusion Injury in Rats

He, Qi; Li, Zhenyu; Meng, Changchang; Wu, Jiangling; Zhao, Yong; Zhao, Jing

doi:10.3390/cells8080897

Cited by 83 publications

(65 citation statements)

References 49 publications

(69 reference statements)

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“…Inhibition of the AMPK/Sirt3 signaling pathway abolished Mfn2-mediated protection on I/R-treated N2a cells through induction of mitochondrial damage. This finding defines a Mfn2/AMPK/Sirt3 axis as a new regulator of mitochondrial homeostasis and cell survival in the context of cardio-cerebrovascular I/R injury (Chen et al, 2019;He et al, 2019). Several protective approaches have been developed to regulate mitochondrial function and attenuate brain/heart damage after I/R injury.…”

Section: Discussionmentioning

confidence: 93%

“…Improvement of mitochondrial biogenesis and promotion of glucose metabolism through activation of Rac2 has been found to sustain brain function after I/R injury (Xia et al, 2020). Parkin-dependent mitophagy is significantly depressed in reperfused brain, and activation of mitophagy sends pro-survival signals to neurons in the context of I/R injury (He et al, 2019). Although extracellular signal-regulated kinase (ERK) has been found to be a regulator of cancer proliferation, inhibition of the ERK signaling pathway through administration of PD98059 significantly protects the brain against mitochondria-mediated apoptosis in I/R injury .…”

Section: Discussionmentioning

confidence: 99%

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RETRACTED: Mfn2 Overexpression Attenuates Cardio-Cerebrovascular Ischemia–Reperfusion Injury Through Mitochondrial Fusion and Activation of the AMPK/Sirt3 Signaling

Liu

Huang

2020

Front. Cell Dev. Biol.

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Mitochondria are potential targets for the treatment of cardio-cerebrovascular ischemiareperfusion (I/R) injury. However, the role of the mitofusin 2 (Mfn2) protein in regulating mitochondrial fusion and cell survival has not been investigated. In the present study, an adenovirus-mediated Mfn2 overexpression assay was performed to understand the effects of Mfn2 on mitochondrial function and cell damage during cardiocerebrovascular I/R injury. After exposure to I/R injury in vitro, the transcription and expression of Mfn2 were significantly downregulated, which correlated with decreased cell viability and increased apoptosis. By contrast, overexpression of Mfn2 significantly repressed I/R-mediated cell death through modulation of glucose metabolism and oxidative stress. Furthermore, Mfn2 overexpression improved mitochondrial fusion in cells, an effect that was followed by increased mitochondrial membrane potential, improved mitophagy, and inhibition of mitochondria-mediated apoptosis. Our data also demonstrated that Mfn2 overexpression was associated with activation of the AMPK/Sirt3 signaling pathway. Inhibition of the AMPK/Sirt3 pathway abolished the protective effects of Mfn2 on I/R-induced cell injury arising from mitochondrial damage. Our results indicate that Mfn2 protects against cardio-cerebrovascular I/R injury by augmenting mitochondrial fusion and activating the AMPK/Sirt3 signaling pathway.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

RETRACTED: Mfn2 Overexpression Attenuates Cardio-Cerebrovascular Ischemia–Reperfusion Injury Through Mitochondrial Fusion and Activation of the AMPK/Sirt3 Signaling

Liu

Huang

2020

Front. Cell Dev. Biol.

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“…Recent study has reported that electroacupuncture improves CI/R injury by activating Pink1/Parkin-induced mitophagy [7]. Pink1/Parkin-mediated mitophagy ameliorates CI/R injury by eliminating ATF4 and NLRP3 inflammasome [8]. However, Bcl-2/E1B 19 kDa-interacting protein 3 (BNIP3) is highly expressed after CI/R, which causes excessive activation of mitophagy, triggers delayed cell death, and aggravates CI/R injury [9].…”

Section: Introductionmentioning

confidence: 99%

LncRNA SNHG14 promotes OGD/R-induced neuron injury by inducing excessive mitophagy via miR-182-5p/BINP3 axis in HT22 mouse hippocampal neuronal cells

Deng

Ren

et al. 2020

Biol Res

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Background Long non-coding RNA (lncRNA) small nucleolar RNA host gene 14 (SNHG14) is associated with cerebral ischemia–reperfusion (CI/R) injury. This work aims to explore the role of SNHG14 in CI/R injury. Methods HT22 (mouse hippocampal neuronal cells) cell model was established by oxygen–glucose deprivation/reoxygenation (OGD/R) treatment. The interaction among SNHG14, miR-182-5p and BNIP3 was verified by luciferase reporter assay. Flow cytometry, western blot and quantitative real-time PCR were performed to examine apoptosis, the expression of genes and proteins. Results SNHG14 and BNIP3 were highly expressed, and miR-182-5p was down-regulated in the OGD/R-induced HT22 cells. OGD/R-induced HT22 cells exhibited an increase in apoptosis. SNHG14 overexpression promoted apoptosis and the expression of cleaved-caspase-3 and cleaved-caspase-9 in the OGD/R-induced HT22 cells. Moreover, SNHG14 up-regulation enhanced the expression of BNIP3, Beclin-1, and LC3II/LC3I in the OGD/R-induced HT22 cells. Furthermore, SNHG14 regulated BNIP3 expression by sponging miR-182-5p. MiR-182-5p overexpression or BNIP3 knockdown repressed apoptosis in OGD/R-induced HT22 cells, which was abolished by SNHG14 up-regulation. Conclusion Our study demonstrates that lncRNA SNHG14 promotes OGD/R-induced neuron injury by inducing excessive mitophagy via miR-182-5p/BINP3 axis in HT22 mouse hippocampal neuronal cells. Thus, SNHG14/miR-182-5p/BINP3 axis may be a valuable target for CI/R injury therapies.

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“…Furthermore, mitophagy is thought to mediate the protective effect of ischemic preconditioning in kidneys by targeting a series of biological events, including damaged mitochondrial clearance, mitophagosome formation, and mitochondrial depolarization [41]. In addition, crucial roles for mitophagy in affording neuroprotection against IR cerebral injury and alleviating metabolic dysfunction have also been reported [20,[42][43][44]. Under tumor-related hypoxic conditions, the activation of mitophagy is involved in assisting tumor cell survival and promoting cancer, while BNIP3-or BNIP3L-mediated mitophagy may act as a suppressor of tumorigenesis and metastasis in breast cancer or xenograft conditions [45][46][47].…”

Section: Discussionmentioning

confidence: 99%

Locally Activated Mitophagy Contributes to a 'Built-In' Protection Against Early Burn-Wound Progression in Rats Following a Regulation of HIF-1α

et al. 2020

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Background: Deep burn wounds undergo a dynamic progression in the initial or periburn area after insults. The zone of stasis has a higher risk of deterioration and is considered a salvageable target for burn-wound progression. Few studies have explored the role of mitochondrial damage in this process and potential "built-in" self-defense within the human body. Methods: A classic "comb" scald rat model was established in this study. Histological and blood-ow observation were processed based on hematoxylin-eosin staining and laser analysis. Oxidative and apoptotic status were analyzed by commercial kits. Transmission electron microscope, immuno uorescence staining, and western blot were applied to detect the mitophagy happened in the zone of stasis and potential regulators. Adenovirus-based gene-silence contributed to determine the role of HIF-1 as a regulatory mediator. Results: We found that burn insults caused typical ischemia and histological deterioration in the zone of stasis, in parallel with increases in oxidative stress and apoptosis. Mitochondrial damage was also involved in the aforementioned changes. Furthermore, we detected typical mitophagy in burn wounds, which was contradictory to the burn-wound conversion. HIF-1 expression was closely related to the level of mitophagy, while BNIP3 and PARKIN are involved downstream. Conclusion: We demonstrate that burn-induced mitochondrial impairment contributes to the mobilization of injurious mechanisms in the zone of stasis and that mitophagy provides a more bene cial way to protect against burn-wound progression via the elimination of damaged mitochondria. Our ndings offer insights into mitochondrial quality control in burn-wound progression and suggest the novel concept that HIF-1 may be a potential therapeutic target due to its possible regulatory effects upstream of BNIP3-or PARKIN-mediated mitophagy. Background Deep thermal burns can cause irreversible tissue damage to the integument that can further progress over 3 days[1]. Dynamic conversion, including expansion and deepening, can be observed in the peripheral zones of initial wounds of partial thickness or full thickness burns from 48 h to 72 h; this is de ned as burn wound progression[1-3]. Jackson described three concentric zones (coagulation, stasis and hyperemia from the center to the outer region) to explain the histopathological changes that occur in early burn wounds[4]. The intermediate zone, which undergoes stasis characterized by edema and slow blood ow, progresses to irrecoverable necrosis without appropriate interventions, and the zone of stasis is also considered salvageable and provides an opportunity to prevent cutaneous wound conversion after burn injury[1,2,5]. Efforts to attenuate the early deterioration of initial burn wounds are of great importance. The burn-induced ischemic status in the zone of stasis is attributed to multiple pathophysiological mechanisms, such as edema, vasoconstriction and hypercoagulability[2,5]. A number of studies have

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Parkin-Dependent Mitophagy is Required for the Inhibition of ATF4 on NLRP3 Inflammasome Activation in Cerebral Ischemia-Reperfusion Injury in Rats

Cited by 83 publications

References 49 publications

RETRACTED: Mfn2 Overexpression Attenuates Cardio-Cerebrovascular Ischemia–Reperfusion Injury Through Mitochondrial Fusion and Activation of the AMPK/Sirt3 Signaling

RETRACTED: Mfn2 Overexpression Attenuates Cardio-Cerebrovascular Ischemia–Reperfusion Injury Through Mitochondrial Fusion and Activation of the AMPK/Sirt3 Signaling

LncRNA SNHG14 promotes OGD/R-induced neuron injury by inducing excessive mitophagy via miR-182-5p/BINP3 axis in HT22 mouse hippocampal neuronal cells

Locally Activated Mitophagy Contributes to a 'Built-In' Protection Against Early Burn-Wound Progression in Rats Following a Regulation of HIF-1α

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